Mechanism Found Linking Hypertension to Diabetes

Hypertension, or high blood pressure, has been closely linked in past research to the development of diabetes. Recent research has found a molecular mechanism that may explain why these conditions, and others, are so closely linked.

Nearly 75 million Americans suffer from hypertension, which is a condition considered to be a high risk factor for type 2 diabetes, as well as heart disease and immune system dysfunction. Hypertension often initially leads to the pre-diabetic condition, insulin resistance, where normal insulin levels secreted by the pancreas are insufficient for proper insulin response. This diminishes the bodies ability to control blood glucose levels.

Spontaneously hypertensive rats (SHRs) were used for the study. Rats with the SHR strain are essentially programmed to develop hypertension. The SHR model is one of the most extensively used animal models for studying various cardiovascular conditions.

The researchers found high levels of enzymes that break down proteins, called proteases, in the bloodstreams of the SHRs. These proteases were observed to break down insulin receptors, which means that the necessary binding of insulin secreted by the pancreas in order to regulate blood glucose levels was no longer possible. This mechanism of proteases, which are present in high numbers due to hypertension, breaking down insulin receptors, could go a long way in explaining why hypertension is such a high risk factor for type 2 diabetes.

It was also shown in the study that high levels of proteases break down a leukocyte receptor known as CD18. Leukocytes bind to the walls of blood vessels in order to fight infections. Therefore, the high levels of proteases in the SHR bloodstreams resulted in suppressed immune system response, in addition to insulin resistance. Some past research has also linked type 2 diabetes and “immune suppression,” and again high protease levels may explain how all of these conditions are connected.

“These results point to a single mechanism that explains multiple and diverse cell dysfunctions encountered in hypertensive rats, and they also suggest that a similar mechanism may be operating in humans suffering simultaneously from hypertension, diabetes, and other metabolic conditions,” says study author Dr. Geert Schmid-Schönbein.

The researchers administered various drugs to see if protease levels could be reduced or controlled in the SHRs. Surprisingly, the common antibiotic doxycycline, which is prescribed for various antibacterial infections, and as an anti-malarial drug, was observed to block the breaking down of protein receptors caused by protease. For the SHRs already suffering from insulin resistance and immune suppression, administration of doxycycline helped bring insulin and leukocyte receptors to normal levels, in effect reversing insulin resistance and immune suppression development.

It’s anticipated that these important results will be followed up on a human model. H. Glenn Bolen, commenting in an editorial for the journal Hypertension, says “even if future studies only support the clear linkage of hypertension to insulin receptor cleavage in the current study of SHRs, this observation should lead to many studies of how these two problems perhaps interact.” This future research, in addition to confirming the mechanism linking hypertension to diabetes and immune suppression, could validate the simple treatment of doxycycline administration as a preventative measure for these conditions.

Source: Defeat Diabetes Foundation: Bolen, Glenn H. “Metalloproteinases Damage the Insulin Receptor to Cause Insulin Resistance in Spontaneously Hypertensive Rats.” Hypertension. June 2008. Graham, Rex. Schmid-Schönbein, Geert. Hypertension news release. June 2008.